What is the next evaluation step for a patient with uncontrolled hypertension on Angiotensin Receptor Blocker (ARB), calcium channel blockers, diuretics, and beta blockers, and eplerenone (an aldosterone antagonist), with an elevated aldosterone-to-renin ratio (ARR)?

Next Evaluation for a Patient with Uncontrolled Hypertension and Elevated Aldosterone-to-Renin Ratio

For a patient with uncontrolled hypertension on multiple antihypertensive medications including eplerenone and an elevated aldosterone-to-renin ratio (ARR) >111, the next step should be confirmatory testing for primary aldosteronism with an intravenous saline suppression test or oral salt-loading test. 1, 2

Understanding the Current Clinical Picture

• The patient has resistant hypertension (uncontrolled despite multiple medications including ARB, calcium channel blocker, diuretics, beta blockers, and eplerenone) 1
• The elevated ARR >111 strongly suggests primary aldosteronism, which is present in up to 20% of patients with resistant hypertension 3, 4
• The patient is already on eplerenone (an aldosterone antagonist), which can affect ARR interpretation but does not rule out primary aldosteronism 2, 5

Diagnostic Algorithm

1. Medication Considerations Before Confirmatory Testing

• Ideally, mineralocorticoid receptor antagonists (eplerenone) should be withdrawn at least 4 weeks before confirmatory testing 2

• Other interfering medications that should be discontinued when feasible include:

  • Beta-blockers (can cause false positives by suppressing renin) 1
  • ARBs (can cause false negatives by increasing renin) 1
  • Diuretics (can cause false negatives) 1

• If medications cannot be safely discontinued, the European Society of Cardiology suggests that testing can still proceed with careful interpretation of results in the context of current medications 1

2. Confirmatory Testing Options

• Intravenous saline suppression test: Administration of 2L of 0.9% saline over 4 hours with measurement of aldosterone before and after 2, 6
• Oral salt loading test: High sodium diet with 24-hour urine collection for aldosterone 2, 3
• Captopril challenge test: Alternative option if the above tests are contraindicated 6

3. Subtype Determination (If Primary Aldosteronism Is Confirmed)

• Adrenal imaging with high-resolution CT or MRI to identify potential adenomas 3, 7
• Adrenal venous sampling (AVS) to distinguish between unilateral and bilateral disease, especially in patients >40 years old 2, 3

Important Considerations and Pitfalls

• Potassium levels: Ensure normal serum potassium before testing, as hypokalemia can suppress aldosterone production and lead to false-negative results 2
• Salt intake: Assess sodium intake before testing, as it affects the ARR interpretation 1, 2
• Eplerenone effect: The current use of eplerenone may be masking the full extent of hyperaldosteronism 5
• False positives: An elevated ARR can occur in low-renin states even without truly elevated aldosterone levels 2, 3
• Confirmation is essential: A positive ARR screening test alone is not diagnostic and requires confirmation before proceeding to invasive procedures 4, 6

Treatment Implications

• If primary aldosteronism is confirmed and subtyped:

  • Unilateral aldosterone-producing adenoma: Consider laparoscopic adrenalectomy 2, 7
  • Bilateral adrenal hyperplasia: Optimize medical therapy with mineralocorticoid receptor antagonists 2, 7

• The current use of eplerenone suggests that primary aldosteronism may have been suspected, but formal diagnosis appears incomplete 5

• Proper diagnosis and targeted treatment can significantly improve blood pressure control and reduce cardiovascular risk 7, 4